دورية أكاديمية
أعرض في EDS

Exome, transcriptome and miRNA analysis don't reveal any molecular markers of TKI efficacy in primary CML patients.

التفاصيل البيبلوغرافية
العنوان: Exome, transcriptome and miRNA analysis don't reveal any molecular markers of TKI efficacy in primary CML patients.
المؤلفون: Lavrov AV; Laboratory of Mutagenesis, Federal State Budgetary Institution, Research Centre for Medical Genetics, Moskvorechie str., 1, Moscow, Russian Federation, 115522. alexandervlavrov@gmail.com.; Department of Molecular and Cellular Genetics, State Budgetary Educational Institution of Higher Professional Education 'Russian National Research Medical University named after N.I. Pirogov' of Ministry of Health of the Russian Federation, Ostrovityanova str., 1, Moscow, Russian Federation, 117997. alexandervlavrov@gmail.com., Chelysheva EY; Scientific and Advisory Department of Chemotherapy of Myeloproliferative disorders, Federal State-Funded Institution National Research Center for Hematology of the Ministry of Healthcare of the Russian Federation, Novy Zykovki proezd, 4, Moscow, Russian Federation, 125167., Adilgereeva EP; Laboratory of Mutagenesis, Federal State Budgetary Institution, Research Centre for Medical Genetics, Moskvorechie str., 1, Moscow, Russian Federation, 115522., Shukhov OA; Scientific and Advisory Department of Chemotherapy of Myeloproliferative disorders, Federal State-Funded Institution National Research Center for Hematology of the Ministry of Healthcare of the Russian Federation, Novy Zykovki proezd, 4, Moscow, Russian Federation, 125167., Smirnikhina SA; Laboratory of Mutagenesis, Federal State Budgetary Institution, Research Centre for Medical Genetics, Moskvorechie str., 1, Moscow, Russian Federation, 115522., Kochergin-Nikitsky KS; Laboratory of Mutagenesis, Federal State Budgetary Institution, Research Centre for Medical Genetics, Moskvorechie str., 1, Moscow, Russian Federation, 115522., Yakushina VD; Laboratory of Mutagenesis, Federal State Budgetary Institution, Research Centre for Medical Genetics, Moskvorechie str., 1, Moscow, Russian Federation, 115522., Tsaur GA; Regional Children Hospital 1, S. Deryabinoy str., 32, Ekaterinburg, Russian Federation, 620149.; Research Institute of Medical Cell Technologies, Soboleva str., 25, Ekaterinburg, Russian Federation, 620905.; Federal State Budgetary Educational Institution of Higher Education, Urals State Medical University of the Ministry of Healthcare of the Russian Federation, Repina str., 3, Ekaterinburg, Russian Federation, 620028., Mordanov SV; Laboratory of Medical Genetics, The Rostov State Medical University, Nahichevansky av., 29, Rostov-on-Don, Russian Federation, 344022., Turkina AG; Scientific and Advisory Department of Chemotherapy of Myeloproliferative disorders, Federal State-Funded Institution National Research Center for Hematology of the Ministry of Healthcare of the Russian Federation, Novy Zykovki proezd, 4, Moscow, Russian Federation, 125167., Kutsev SI; Laboratory of Mutagenesis, Federal State Budgetary Institution, Research Centre for Medical Genetics, Moskvorechie str., 1, Moscow, Russian Federation, 115522.; Department of Molecular and Cellular Genetics, State Budgetary Educational Institution of Higher Professional Education 'Russian National Research Medical University named after N.I. Pirogov' of Ministry of Health of the Russian Federation, Ostrovityanova str., 1, Moscow, Russian Federation, 117997.
المصدر: BMC medical genomics [BMC Med Genomics] 2019 Mar 13; Vol. 12 (Suppl 2), pp. 37. Date of Electronic Publication: 2019 Mar 13.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: BioMed Central Country of Publication: England NLM ID: 101319628 Publication Model: Electronic Cited Medium: Internet ISSN: 1755-8794 (Electronic) Linking ISSN: 17558794 NLM ISO Abbreviation: BMC Med Genomics Subsets: MEDLINE
أسماء مطبوعة: Original Publication: London : BioMed Central
مواضيع طبية MeSH: Exome* , Transcriptome*, Leukemia, Myelogenous, Chronic, BCR-ABL Positive/*drug therapy , MicroRNAs/*metabolism , Protein Kinase Inhibitors/*therapeutic use, Adult ; Aged ; Biomarkers, Tumor/genetics ; Biomarkers, Tumor/metabolism ; Female ; Genotype ; Humans ; Imatinib Mesylate/therapeutic use ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/diagnosis ; Male ; Middle Aged ; Polymorphism, Genetic ; Prognosis ; Treatment Outcome ; Young Adult
مستخلص: Background: Approximately 5-20% of chronic myeloid leukemia (CML) patients demonstrate primary resistance or intolerance to imatinib. None of the existing predictive scores gives a good prognosis of TKI efficacy. Gene polymorphisms, expression and microRNAs are known to be involved in the pathogenesis of TKI resistance in CML. The aim of our study is to find new molecular markers of TKI therapy efficacy in CML patients.
Methods: Newly diagnosed patients with Ph+ CML in chronic phase were included in this study. Optimal and non-optimal responses to TKI were estimated according to ELN 2013 recommendation. We performed genotyping of selected polymorphisms in 62 blood samples of CML patients, expression profiling of 33 RNA samples extracted from blood and miRNA profiling of 800 miRNA in 12 blood samples of CML patients.
Results: The frequencies of genotypes at the studied loci did not differ between groups of patients with an optimal and non-optimal response to TKI therapy. Analysis of the expression of 34,681 genes revealed 26 differently expressed genes (p < 0.05) in groups of patients with different TKI responses, but differences were very small and were not confirmed by qPCR. Finally, we did not find difference in miRNA expression between the groups.
Conclusions: Using modern high-throughput methods such as whole-exome sequencing, transcriptome and miRNA analysis, we could not find reliable molecular markers for early prediction of TKI efficiency in Ph+ CML patients.
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فهرسة مساهمة: Keywords: Chronic myeloid leukemia; Exome; TKI efficacy; Transcriptome; miRNA analysis
المشرفين على المادة: 0 (Biomarkers, Tumor)
0 (MicroRNAs)
0 (Protein Kinase Inhibitors)
8A1O1M485B (Imatinib Mesylate)
تواريخ الأحداث: Date Created: 20190316 Date Completed: 20200513 Latest Revision: 20200513
رمز التحديث: 20221213
مُعرف محوري في PubMed: PMC6416830
DOI: 10.1186/s12920-019-0481-z
PMID: 30871622
قاعدة البيانات: MEDLINE
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